Title:Association between Matrix Metalloproteinases, Their Tissue Inhibitor and White Matter Lesions in Mild Cognitive Impairment
Volume: 17
Issue: 6
Author(s): Noriyuki Kimura*, Miki Aikawa, Kasumi Etou, Yasuhiro Aso and Etsuro Matsubara
Affiliation:
- Department of Neurology, Oita University, Faculty of Medicine, Graduate School of Medicine, Oita 879-5593,Japan
Keywords:
Brain amyloid burden, cognitive function, matrix metalloproteinases, mild cognitive impairment, tissue inhibitor of
metalloproteinases, white matter lesions.
Abstract:
Background: White matter lesions are frequently found in mild cognitive impairments and
Alzheimer’s disease. Matrix metalloproteinases and the tissue inhibitor of metalloproteinases are implicated
in amyloid-β catabolism and blood brain barrier permeability. However, it remains unclear
whether they are associated with white matter lesions in Alzheimer’s disease.
Objective: The aim of this study was to examine the association of matrix metalloproteinases and tissue
inhibitor of metalloproteinases with white matter degeneration in subjects with amyloid-positive mild
cognitive impairment.
Methods: Thirty subjects with amnestic mild cognitive impairment (14 men and 16 women; mean age,
75.6 ± 5.8 years) underwent magnetic resonance imaging, 11C-Pittsburgh Compound B positron emission
tomography, and 18F-fluorodeoxyglucose positron emission tomography. Levels of plasma matrix
metalloproteinases and tissue inhibitor of metalloproteinases were measured using multiplex assays. All
subjects had an abnormal brain amyloid burden. Subjects were divided into two groups according to the
presence of white matter lesions using the Fazekas scale. Cognitive function testing results i.e., mean
11C-Pittsburgh Compound B and 18F-fluorodeoxyglucose uptake, concentrations of matrix metalloproteinases
and tissue inhibitor of metalloproteinases, and matrix metalloproteinases/tissue inhibitor of metalloproteinases
ratios were compared between the groups. Correlation analysis was conducted to investigate
the association between Fazekas scale score and clinical and neuroimaging variables as well as
concentrations of matrix metalloproteinases and tissue inhibitor of metalloproteinases.
Results: Matrix metalloproteinases-2, -8, and -9 levels, matrix metalloproteinases-2/ tissue inhibitor of
metalloproteinases-2, matrix metalloproteinases-8/ tissue inhibitor of metalloproteinases-1, and matrix
metalloproteinases-9/tissue inhibitor of metalloproteinases-1 significantly increased and tissue inhibitor
of metalloproteinases-1 and-2 levels significantly decreased in the group with white matter lesions compared
with the group without white matter lesions. Matrix metalloproteinases-2, -8, and -9 levels correlated
positively and tissue inhibitor of metalloproteinases-1 and -2 levels correlated negatively with
Fazekas scale score.
Conclusion: Plasma matrix metalloproteinases-2, -8, -9 and tissue inhibitor of metalloproteinases-1 and
-2 levels are associated with white matter lesions in the mild cognitive impairment stage of Alzheimer’s
disease.
